Update: IONIS-DMPKRx Phase 1/2a Study

Ionis Pharmaceuticals recently announced completion of the IONIS-DMPKRx Phase 1/2a clinical trial, and stated that it expects to have analysis of the data collected through that study completed by early January 2017. The study was designed to evaluate the safety and tolerability of multiple doses of an investigational compound, IONIS-DMPKRx, in adult patients with DM1.

The study was a randomized, placebo-controlled, dose-escalation Phase 1/2 clinical trial in approximately 48 adult patients with DM1. The original clinical trial design included the analysis of doses ranging from 100–400mg and, based on safety, was later expanded to include a 600mg dose group.

IONIS-DMPKRx is designed to reduce the production of toxic dystrophia myotonic-protein kinase (DMPK) RNA in cells, including muscle cells, for the treatment of DM1. IONIS-DMPKRx was the third generation 2.5 drug to enter clinical development for Ionis and the first designed to modulate a target in muscle tissue.

The clinical trial was primarily focused on safety, and was also designed to determine the approximate therapeutic dose of an antisense drug needed to affect muscle. The study included multiple exploratory endpoints, such as evaluations on muscle strength, myotonia, functional tests that include the 6 minute walk test (6MWT), and even a patient-reported outcomes questionnaire (Myotonic Dystrophy Health Index, SF-36, CGI-I).

Another goal was to standardize these tests across multiple sites, familiarize the patients with the procedures, and determine whether the results could be reproduced. Due to the heterogeneity of DM1, individual-based analysis will be needed to better understand the relationship between the effects of the drug, splicing changes, and functional outcomes changes. Currently, both the safety and exploratory data are being analyzed and that data will provide important information for the design of future studies in DM1.